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PLoS One. 2008 Oct 6;3(10):e3354. doi: 10.1371/journal.pone.0003354.

A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans.

Author information

1
Laboratoire de Génétique, Signalisation et Cancer, Université Claude Bernard Lyon 1, CNRS UMR5201 Domaine Rockefeller, Lyon, France.

Erratum in

  • PLoS ONE. 2009;4(1). doi: 10.1371/annotation/8b010ad6-34d5-45fc-9bc2-c82a7370ebc7.

Abstract

The PTEN tumour suppressor encodes a phosphatase, and its daf-18 orthologue in Caenorhabditis elegans negatively regulates the insulin/IGF-1 DAF-2 receptor pathway that influences lifespan in worms and other species. In order to identify new DAF-18 regulated pathways involved in aging, we initiated a candidate RNAi feeding screen for clones that lengthen lifespan. Here, we report that smg-1 inactivation increases average lifespan in a daf-18 dependent manner. Genetic analysis is consistent with SMG-1 acting at least in part in parallel to the canonical DAF-2 receptor pathway, but converging on the transcription factor DAF-16/FOXO. SMG-1 is a serine-threonine kinase which plays a conserved role in nonsense-mediated mRNA decay (NMD) in worms and mammals. In addition, human SMG-1 has also been implicated in the p53-mediated response to genotoxic stress. The effect of smg-1 inactivation on lifespan appears to be unrelated to its NMD function, but requires the p53 tumour suppressor orthologue cep-1. Furthermore, smg-1 inactivation confers a resistance to oxidative stress in a daf-18-, daf-16- and cep-1-dependent manner. We propose that the role of SMG-1 in lifespan regulation is at least partly dependent on its function in oxidative stress resistance. Taken together, our results unveil a novel role for SMG-1 in lifespan regulation.

PMID:
18836529
PMCID:
PMC2556085
DOI:
10.1371/journal.pone.0003354
[Indexed for MEDLINE]
Free PMC Article

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